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Evidence for familial aggregation of tremor in normal individuals

From the Gertrude H. Sergievsky Center (Drs. Louis and Ottman) and Department of Neurology (Drs. Louis, Ford, and Frucht), College of Physicians and Surgeons, Columbia University; Department of Statistics (Dr. Rabinowitz), Columbia University; Mailman School of Public Health, Epidemiology Division (Dr. Ottman), Columbia University, New York, NY; and the Epidemiology of Brain Disorders Research Department, New York State Psychiatric Institute (Dr. Ottman), New York, NY.

Address correspondence and reprint requests to Dr. Elan D. Louis, Unit #198, Neurological Institute, 710 West 168th Street, New York, NY 10032.

BACKGROUND: Tremor occurs in most normal individuals, and this tremor may offer basic clues about the mechanisms of neuromuscular control. It is not known whether genetic factors influence the magnitude of tremor in normal families.

OBJECTIVE: To assess the familial aggregation of tremor in normal families.

METHODS: Control subjects from the Washington Heights–Inwood community in northern Manhattan, NY, were enrolled in a family study. These subjects and their first- and second-degree relatives underwent a videotaped tremor examination. Two neurologists rated the severity of tremor on the videotaped examination, assigning a total tremor score (0 to 36 [maximum]). Associations between the control subjects’ and their relatives’ total tremor scores were assessed using correlation coefficients and linear regression analysis. In addition, maximum likelihood methods were used to fit a linear mixed-effects model to the total tremor scores of probands and their siblings, after excluding any relatives with essential tremor.

RESULTS: There were 56 control subjects and 226 relatives. Tremor was clinically detectable in 221 (97.8%) of 226 relatives. There was an association between the control subjects’ total tremor scores and those of their siblings (r = 0.40; p = 0.018), those of all of their first-degree relatives (siblings and children combined, r = 0.20; p = 0.037), but not those of their second-degree relatives (r = 0.002; p = 0.99). In analyses of probands and normal siblings, the estimate of the variance of the family-specific component of the age-adjusted total tremor score was different from zero (p < 0.005), and the family specific component was estimated to account for 52% of the variability in the scores.

CONCLUSIONS: Tremor aggregates in normal families, suggesting that genetic factors may contribute to its etiology. Other studies might be designed by investigators to identify these genes through genetic linkage or association analysis. Identification of such genes would help to elucidate the mechanisms underlying this ubiquitous condition.